Altered physiochemical properties of the deoxyribonucleic acid-mitomycin C complex. Evidence for the conformational change in deoxyribonucleic acid.
Binding of the antibiotic mitomycin C to sonicated calf thymus DNA results in increased viscosity and an unaltered sedimentation constant of DNA. Flow dichroism measurements of the mitomycin C-DNA complex indicate that the 310-nm absorbance vector of the chromophore of the bound drug is oriented at approximately 57.2 degrees relative to the helix axis. A conclusion drawn from these results is that mitomycin C does not intercalate between base pairs, but rather, it is bound in one of the grooves. Binding of mitomycin C causes a number of changes which are DNA size dependent: (1) increased viscosity of sonicated, decreased viscosity of nonsonicate DNA; (2) unaltered sedimentation rate of sonicated, increased rate of nonsonicated DNA; (3) reduced electrophoretic mobility of nonsonicated DNA; (4) electron microscopic appearance of sonicated DNA-mitomycin complexes which is similar to that of control, while nonsonicated DNA complexes which display highly coiled, looped structures not seen in control nonsonicated DNA. These size-dependent effects are interpreted as indicative of conformational distortion of DNA at rare intervals, caused by a minor fraction of total bound mitomycin. The parallel used of sonicated and nonsonicated DNA as probes for certain effects of drug binding may be useful for detecting this type of phenomenon in general.
D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D066298:In Vitro Techniques; D007364:Intercalating Agents; D016685:Mitomycin; D008937:Mitomycins / Q000378:metabolism* / Q000494:pharmacology; D009690:Nucleic Acid Conformation / Q000187:drug effects; D014783:Viscosity
D007364:Intercalating Agents; D008937:Mitomycins; D016685:Mitomycin; D004247:DNA